As he was an illegitimate child, he could not enter the college of physicians. Despite this he was a relatively successful physician. The first description of Typhoid fever is attributed to him.

Today he is mainly known as a mathematician. He made some discoveries in algebra. He proposed ways to solve cubic and quartic equations. Niccolò Fontana Tartaglia told him about the solution of one particular cubic equation, . This caused a long fight. His student Lodovico Ferrari solved the quartic equations. Cardano also speaks about imaginary numbers in the same book, Ars Magna. He did not completely understand what they were like though.

Cardano was often short of money. He gambled. A book of his, called Liber de ludo aleae (aproximately translates to as Book on the game of chances) contains the first systematic treatment of probability, as well as a section on how to cheat. He wrote it in the 1560s, but it was only published after his death, in 1663.

He invented various things. He also thought that perpetual motion was impossible, except for stars.